The medical and economic impact of coronary artery disease (CAD), one of the leading causes of death today in the U.S.. is staggering. A clear need exists for the early identification of individuals at risk for developing premature CAD. Today, research studies investigating the relationship between potentially predisposing genes and CAD are limited by their capacity to handle sufficient quantities of genetic data in a cost- effective and reliable fashion. In this Phase I proposal, we propose to develop a genotyping system, based on our solid-phase GBA(TM) technology which would enable the simultaneous analysis of multiple suspected CAD polymorphisms in a single reliable, informative biochemical format. Feasibility for developing this system will be demonstrated by execution of the following three aims - AIM I: Rapid, cost-effective development of GBA(TM) reagents for 5 polymorphisms found within 4 CAD predisposition genes (apolipoprotein E, methylenetetrahydrofolate reductase. angiotensinogen, and lipoprotein lipase): AIM 2: Accurate, informative, and cost-effective GBA(TM) genotyping of these polymorphisms in a limited population study, and AIM 3: Assessment and planning of Phase II objectives. We propose that a Phase II GBA(TM)-based clinical research test could ultimately have direct impact on individuals at risk for developing premature CAD by dramatically facilitating research efforts.Proposed commercial application:The major commercial application far the technology developed under this proposal will be a clinical research testing system designed for the simultaneous analysis of multiple CAD predisposition genes in a single informative and reliable biochemical format. A longer term commercial goal would be a clinical test with these features with direct prognostic utility to patients at risk for developing coronary artery disease.National Institute of Heart, Lung, and Blood Institute (NHLBI)
